A multiparameter analysis of the perfused rat heart: responses to ischemia, uncouplers and drugs

In perfused rat hearts alterations of aortic flow and mitochondrial membrane potential resulting from uncoupling of oxidative phosphorylation, hypoxia and treatment with a cardioprotective drug (2-mercaptopropionylglycine (MPG) have been studied. Mitochondrial membrane potential was followed by surface fluorimetry on DASPMI stained hearts. This fluorochrome specifically stains mitochondria in living cells; fluorescence intensity is related to the electrochemical gradient. Aortic flow turned out to be a much more sensitive indicator of heart function than ventricular pressure or mitochondrial membrane potential. No direct relationship exists between mitochondrial membrane potential and ATP production under the different metabolic conditions. Two phases of hypoxic mitochondrial damage have been deduced: the first results in derangement of ATP synthases while membrane potential is maintained, the second in irreversible damage of mitochondrial membranes with loss of membrane potential.